Currently, most low permeability reservoirs are developing by water flooding; its development effect becomes worse when the water cut reaches a high period at the later stage of water flooding development. In this situation, the CO2 flooding development method becomes a more effective method of enhanced oil recovery. The major difference between CO2 injection and other gas injections is that CO2 has a much higher solubility in water. Therefore, CO2 solubility in water cannot be ignored in CO2 flooding, especially after water flooding when water saturation has increased significantly. In this article, some five-spot well group numerical compositional mechanism models were built based on the basic geological and fluid parameters of a low permeability reservoir in Xinjiang Oilfield. The numerical simulation of CO2 flooding was applied to analyze the influence on the enhanced oil recovery, CO2 breakthrough time, and geological sequestration of different factors, including salinities, water saturation, gravity effect, and plane heterogeneity.